What does this research mean for the field?

The FVB/N mouse strain fed a western-style diet for eight months most faithfully recapitulates human non-alcoholic steatohepatitis (NASH) pathology and associated metabolic comorbidities compared to other common inbred strains. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

March 22, 2023Scientific ReportsOpen Access

Mouse strain-dependent variation in metabolic associated fatty liver disease (MAFLD): a comprehensive resource tool for pre-clinical studies

Q: What is the clinical evidence from this study?

Study design: Other. Population: Metabolic associated fatty liver disease (MAFLD) and Non-alcoholic steatohepatitis (NASH). Intervention: Western-style diet enriched in fat, sucrose, fructose and cholesterol vs. Rodent chow diet. Primary outcome: Prevalence of NASH, liver fibrosis, and metabolic comorbidities.

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Key result

FVB/N mice fed a 32-week western diet best replicate human NASH and metabolic comorbidities.

or 32

Why the study?

There is a lack of adequate mouse models of NASH that also show metabolic comorbidities commonly observed in NASH patients, hindering pre-clinical to clinical translation of therapies.

Population

Eight common inbred mouse strains fed western-style diet

Comparison

Comparison among eight mouse strains under western-style diet

Design

Pre-clinical comparative study

Authors

HKHamzeh KarimkhanlooDiscovery Institute SKStacey N. KeenanThe University of Melbourne JBJacqueline BaylissThe University of Melbourne

Discussion

Member takes

Implication

Early-phase signals in NASH warrant larger trials; leaves open whether histologic benefits will translate to approved therapy.

Structured PICO

Population

Male mice from eight common inbred strains fed a western-style diet or chow for 30-32 weeks to evaluate susceptibility to diet-induced NASH and metabolic comorbidities.

Intervention

Western-style diet enriched in fat, sucrose, fructose and cholesterol for eight months

Comparator

Comparison among the eight different mouse strains

Outcome

NASH pathology and deep metabolic profiling (hepatic lipid metabolism, obesity, glycaemic control, insulin sensitivity, dyslipidaemia, adipose tissue lipolysis, systemic inflammation, whole-body energy metabolism)surrogate

The FVB/N mouse strain fed a western-style diet for 8 months is an optimal preclinical model for studying MAFLD and NASH with associated metabolic comorbidities.

Limitations

Ex vivo liver slice experimental system lacks hormonal regulation and an integrated in vivo response.
A longer feeding regime and/or modulation of diet composition might provide a better model for advanced NASH and more severe liver fibrosis.
Only male mice were used, warranting future studies in female mice.

Cite This Study

Karimkhanloo et al. (2023) studied Metabolic associated fatty liver disease (MAFLD) and Non-alcoholic steatohepatitis (NASH). Western-style diet enriched in fat, sucrose, fructose and cholesterol vs. Rodent chow diet was evaluated on Prevalence of NASH, liver fibrosis, and metabolic comorbidities. The FVB/N mouse strain fed a western-style diet for 32 weeks most faithfully recapitulates human NASH pathophysiology and predominant metabolic comorbidities, including obesity and insulin resistance.

synapsesocial.com/papers/6aae352789ab2fb7591647fc https://doi.org/10.1038/s41598-023-32037-1

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March 22, 2023Scientific ReportsOpen Access

Mouse strain-dependent variation in metabolic associated fatty liver disease (MAFLD): a comprehensive resource tool for pre-clinical studies

View Full Paper

Ask AI

Bookmark

Key result

FVB/N mice fed a 32-week western diet best replicate human NASH and metabolic comorbidities.

or 32

Why the study?

There is a lack of adequate mouse models of NASH that also show metabolic comorbidities commonly observed in NASH patients, hindering pre-clinical to clinical translation of therapies.

Population

Eight common inbred mouse strains fed western-style diet

Comparison

Comparison among eight mouse strains under western-style diet

Design

Pre-clinical comparative study

Authors

HKHamzeh KarimkhanlooDiscovery Institute SKStacey N. KeenanThe University of Melbourne JBJacqueline BaylissThe University of Melbourne

Discussion

Member takes

Implication

Early-phase signals in NASH warrant larger trials; leaves open whether histologic benefits will translate to approved therapy.

Structured PICO

Population

Male mice from eight common inbred strains fed a western-style diet or chow for 30-32 weeks to evaluate susceptibility to diet-induced NASH and metabolic comorbidities.

Intervention

Western-style diet enriched in fat, sucrose, fructose and cholesterol for eight months

Comparator

Comparison among the eight different mouse strains

Outcome

The FVB/N mouse strain fed a western-style diet for 8 months is an optimal preclinical model for studying MAFLD and NASH with associated metabolic comorbidities.

Limitations

Ex vivo liver slice experimental system lacks hormonal regulation and an integrated in vivo response.
A longer feeding regime and/or modulation of diet composition might provide a better model for advanced NASH and more severe liver fibrosis.
Only male mice were used, warranting future studies in female mice.

Cite This Study

synapsesocial.com/papers/6aae352789ab2fb7591647fc https://doi.org/10.1038/s41598-023-32037-1

Also Consider

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